The aim of this study is to find alloantisera directed against the cell surface antigenic specificities of murine lymphocytes and tumor cells. To this end we are now using the cell fusion method to produce monoclonal antibodies and have produced antibodies to Lyt-2.1, Ly-6.2, Ly-9.2, Ly-15.2, Qa-2, H-2 and Ia alloantigens. We are currently endeavoring to produce monoclonal antibodies to the other alloantigens. The monoclonal antisera have been characterized by strain distribution, including congenic and recombinant inbred strains, tissue distribution, and are currently being examined with regard to distribution on T cell subsets includdng the T-helper, T-graft-rejection, T-delayed hypersensitivity and T-suppressor cells. In addition, the monoclonal antisera are being tested upon a number of tumors. While the use of monoclonal antisera has enormous advantages in this area, it is of interest that most of the results confirm those already found with conventional antisera. However, certain tumors are positive with conventional antisera and negative with monoclonal antisera, indicating the complexity of the conventional antisera and the presence of additional antibodies. One interesting finding has been the in vivo activity of monoclonal Lyt-1.1 antibodies which suppresses the immune response the same as described for xenogeneic antilymphocyte serum.